- Email: [email protected]
Ruling out Ingelfinger?
Cobbe SM, Ford I, et al. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. N Engl J Med 1995; 333: 1301-07. Thompson GR. Angiographic trials of lipid-lowering therapy: end of an era? Br Heart J 1995; 74: 343-48. Petursson KK, Jonmundsson EH, Brekkan A, Hardarson T. Angiographic predictors of new coronary occlusions. Am HeartJ 1995; 129: 515-20. Nissen SE, Gurley JC, Booth DC, et al. Differences in ultravascular plaque morphology in stable and unstable patients. Circulation 1991; 84: II: 436. Shiomi M, Tsukaka T, Yata T, et al. Reduction of serum cholesterol levels alters lesional composition of atherosclerotic plaques: effect of pravastatin sodium on atherosclerosis in mature WHHL rabbits. Arterioscl Thromb Vasc Biol 1995; 15: 1938-95.
Shepherd J,
8
9
10
11
12
Of bites and body odour anybody who has sat by a campfire on a warm summer evening wondering why he or she was selectively being eaten alive by mosquitoes and other winged creatures, the answer might lie in the body odour. Support for the idea is provided by a recent study in Tanzania’ in which three volunteers slept for 9 nights in separate tents outfitted with a mosquito entrance and two exit traps. Each night volunteers slept in the same tent, in the same bed, and under the same unimpregnated bed net, but over the 9 nights they moved between three different sites. Analysis of the mosquito catches showed that one of the volunteers was significantly less attractive to two Anopheles and one Culex species than were the
short-range, insect orientation for landing on skin is largely visual with contributions from local body heat and humidity. Other factors that have been suggested to influence host selection by mosquitoes include age (adults are more attractive than children), and sex (men more than women)/" Also, there seems to be a direct relation between the size of the host and the number of bites received. Finally, there is evidence for species-specific attractiveness for human beings." So, a large person with an irresistible odour, especially a man huffing and puffing while jogging in dark-coloured shorts through a mosquitoinfested area, is likely to be invited for dinnerunfortunately, to be the main course.
Jay S Keystone Tropical Disease Unit, University of Toronto, Ontario, Canada
For
other
The authors concluded that three of the mosquito species must have selected their hosts on a particular blend of human odours. The effect of expired carbon dioxide, a known mosquito attractant, was discounted since the three volunteers were of approximately the same weight, size, and age. Recent experiments using a wind-tunnel bioassay have suggested that human skin microflora might be responsible for producing compounds that attract mosquitoes.2 Human beings have been shown to have varying concentrations and species of skin bacteria resulting in the production of varying amounts of volatile substances that act as mosquito attractants. Earlier studies in blackflies, the "national insect" of Canadian wilderness areas, have shown that sweat, especially from below the waist, was attractive.3 Because trousers were more attractive to flies than were shirts, it has been suggested that the apocrine sweat glands of the groin region might be involved in producing the attractant compounds. Llactic acid and another unidentified compound, isolated from acetone washings to human skin, have been reported to act as attractants for mosquitoes-the differential attractiveness of human beings for Aedes aegypti mosquitoes was related to the amount of L-lactic acid recovered from skin washings, although lactic acid alone was not attractive without a carbon dioxide component in the airstream.’ A skin-produced mosquito attractant that is not dependent on carbon dioxide has also been identified.’ The receptor site for L-lactic acid seems to be a sensory apparatus on mosquito antennae.6 Before applying insect repellent to erogenous zones, readers should keep in mind that odour is not the only factor that attracts flying insects.’ Long-range attractant stimuli for mosquitoes may include movement and colour of clothing, especially dark colours. Carbon dioxide takes over the mid-range as the primary directing stimulus. At two.
1
Knols BGJ, de Jong R, Takken W. Differential attractiveness of isolated humans to mosquitoes in Tanzania. Trans R Soc Trop Med Hyg
2
Knols BGJ, de
1995; 89: 604-06.
Jong R, Takken W. Trapping system for testing olfactory responses of the malarial mosquito Anopheles gambiae in
a
wind tunnel. Med Vet Entomol 1995; 8: 386-88. 3 Thompson BH. Studies on the attraction of Simulium damnosum to its hosts. The nature of substances of the human skin responsible for attractant olfactory stimuli. Tropenmed Parasitol 1976; 27: 83-90. 4 Acree F, Turner RB, Gouck HK, Beroza M, Smith N. L-lactic acid: a mosquito attractant isolated from humans. Science 1968; 161: 1346-47. 5 Schreck CE, Smith N, Carlson DA, Price GD, Haile D, Goodwin DR. A material isolated from human hands that attracts female mosquitoes. J Chem Ecol 1970; 8: 429-38. 6 Davis EE, Sokolove PG. Lactic acid-sensitive receptors on the antennae of the mosquito Aedes aegypti. J Comp Physiol 1976; 105: 43-54. 7 Sutcliffe JF. Black fly host location: a review. Can Zool 1986; 64: 1041-53. 8 Port GR, Boreham PFL, Bryan JH. The relationship of host size to feeding by mosquitoes of the Anopheles gambiae Giles complex (Diptera culicidae). Bull Entomol Res 1980; 70: 133-44. 9 Gilbert IH, Gouck HK, Smith N. Attractiveness of men and women to Aedes aegypti and relative protection time obtained with DEET. Florida Entomol 1996; 49: 53-66. 10 Knols BGJ, Takken W, Charwood JD, de Jong R. Species-specific attraction of Anopheles mosquitoes (Dipeter: Culicidae) to different humans in south-east Tanzania. Proc Exp Appl Entomol 1995; 6: 201-06.
Ruling out Ingelfinger? world devoid of the "Ingelfinger rule". Could the medical community live comfortably without this grim warning from journal editors to prospective authors that a manuscript will be considered for publication only "if its substance has not been submitted or published elsewhere".’ The consequences of discarding Ingelfinger’s legacy would, argue many proponents of the rule, be catastrophic. Research would be disseminated by investigators according to the demands of the media, independent of careful scrutiny by journal editors and their peer reviewers. Once gathered and analysed, new data would be released to the press by status-seeking researchers and media-hungry institutions. Peer review would be subverted, fraudulent research might be encouraged, and the traditional processes of validating new work would be abandoned. Its proponents argue that the Ingelfinger rule protects the integrity of the scientific process, it is "essential to quality control", and it acts as a brake on investigators who "may unconsciously misrepresent their work or exaggerate its importance".’1
Imagine
a
1423
The rule expresses an agreement between the journal’s editor and the investigators. (It differs from the embargoan agreement between journalists and the editor-which aims to coordinate the simultaneous release of information contained in the journal to subscribers and the public.2) The Ingelfinger rule has been embraced by the International Committee of Medical Journal Editors’ and it has now found a new lease of life with the advent of the Internet. As with any good rule, there are exceptions. First, "presentations at scientific meetings and all published abstracts, as well as any media coverage based on them" are exempt.’ Second, data released as part of a national clinical alert are also acceptable, although authors may find that journal editors still object to full disclosure of data even in these circumstances. Third, there are results presented "in the course of governmental deliberations".’ And finally, data can be divulged by negotiation between authors and editors if "their findings are of such urgent concern that they should be released before publication".’ A recent example of this last escape clause was the early release of the finding of an association between vitamin A intake and cranial neural crest defects,6 which was agreed with the editors of the New England Journal of Medicine. The Lancet has recently drawn attention to the importance of linking public-health alerts to the simultaneous publication of peer-reviewed datawhich can be achieved by rapid peer review and an efficient publication process. But I find it hard to counter the view of Steven Rosenberg,8 who has written persuasively that "I think this whole involvement of journals in trying to control what doctors and scientists say to the press is wrong ... The journal should be publishing a scientific or medical article strictly on its merit: if it’s got merit, it should be published and, if not, it shouldn’t. Whether someone has talked to the press about it before shouldn’t play a role". In two articles, the second of which appears in this week’s issue, Lawrence Altman, medical correspondent of the New York Times, constructs the history of the Ingelfinger rule and examines the validity of the assumptions that underlie it. He finds the key premise supporting the argument for this partial gagging clause on researchers-namely, the power of peer review to validate a research paper-to be wanting in credibility. This observation is not new; although those of us who handle peer review know how much manuscripts change during their review. The lack of clear proof for the value of this process remains the impetus behind research into journal activities. Ingelfinger would surely have countered that a newspaper reporter should be expected to squeal at the editor’s prohibitive incursion into journalistic territory. But Altman also levels a more serious charge: that the journal editor’s role, as Ingelfinger admitted, is selfserving, embodying the commercial need of a journal to control the dissemination of research information. Ingelfinger acolytes might argue that this challenge merely reflects the healthy competition that exists between journalists and editors, both groups wishing to scoop the other. Publication in a peer-reviewed journal does not guarantee truth, as numerous examples of published fraudulent research prove.9 The ultimate validity of a
1424
research paper depends on the reproducibility of its results. Editorial review, external peer review, and subsequent published correspondence are critical filters in the process of validation but they can provide only incomplete quality control. Validation is not an event that is governed by journal editors, it is an iterative process of careful analysis and attempts at experimental refutation. Is it time to revoke the Ingelfinger rule? For those who believe that the rule reflects responsible editorial practice and a concern for quality, and does no harm, the answer will clearly be no. But those who see publication in a journal as only one small part of the scientific process, and one with no intrinsic claim to truth, may be less certain. One might predict that after an interval during which some researchers will be tempted to approach journalists directly before submitting their work to a scientific journal, the lessons of hyped reports and misleading interpretations are likely to encourage authors to adopt a policy of self-censorship until final publication. Selfregulation seems preferable to threats by editors to deny
publication. For research that bears directly on public-health issues, such as the safety of a drug, the responsible course of action is to publish, simultaneously with the alert, data on which the warning has been based. But for the vast majority of research, why should journal editors attempt to exert decisive control over its release? The commercial argument fails not only because there will always be an archival need, print or electronic, for journals but also because most research will be of little immediate interest to journalists and the public. And the personality of many journals, which secures their loyal readership, depends on more than the publication of primary research alone. With arguments such as these so finely balanced, The Lancet wishes to place a serious question mark over the Ingelfinger rule and to invite comment from readers, including researchers, editors, and journalists, as to the contemporary value of this injunction. My inclination is to rescind the rule, although this action would have little effect on authors if other journals chose to maintain their strict line. I cannot conceive of an instance when we would reject a paper only because of its previous publicity. Perhaps the question boils down simply to this: can editors trust investigators to report their research responsibly, and if not, why not? Richard Horton The Lancet, London, UK 1.
Angell M, Kassirer JP.
The
Ingelfinger rule revisited. N Engl J Med
1991; 325: 1371-73. 2. Kassirer JP, Angell M. Violations of the embargo and a new policy on early publicity. N Engl J Med 1994; 330: 1608-09. 3. International Committee of Medical Journal Editors. Uniform
4.
requirements for manuscripts submitted to biomedical journals. Philadelphia: American College of Physicians, 1994. Kassirer JP, Angell M. The Internet and the Journal. N Engl J Med 1995; 332: 1709-10.
5.
6. 7.
8.
9.
Altman LK. Doctors are warned about eye treatment. New York Times 1995; October 11: A17. Choo V. High-dose retinol associated with birth defects. Lancet 1995; 346: 1027. Editorial. Sensible alerts. Lancet 1995; 346: 1569. Cantigny conference series. Medicine and the media: a changing relationship. Chicago: Robert R McCormick Tribune Foundation, 1994: 20. Editorial. Dealing with deception. Lancet 1996; 347: 843.
Shepherd J,
8
9
10
11
12
Of bites and body odour anybody who has sat by a campfire on a warm summer evening wondering why he or she was selectively being eaten alive by mosquitoes and other winged creatures, the answer might lie in the body odour. Support for the idea is provided by a recent study in Tanzania’ in which three volunteers slept for 9 nights in separate tents outfitted with a mosquito entrance and two exit traps. Each night volunteers slept in the same tent, in the same bed, and under the same unimpregnated bed net, but over the 9 nights they moved between three different sites. Analysis of the mosquito catches showed that one of the volunteers was significantly less attractive to two Anopheles and one Culex species than were the
short-range, insect orientation for landing on skin is largely visual with contributions from local body heat and humidity. Other factors that have been suggested to influence host selection by mosquitoes include age (adults are more attractive than children), and sex (men more than women)/" Also, there seems to be a direct relation between the size of the host and the number of bites received. Finally, there is evidence for species-specific attractiveness for human beings." So, a large person with an irresistible odour, especially a man huffing and puffing while jogging in dark-coloured shorts through a mosquitoinfested area, is likely to be invited for dinnerunfortunately, to be the main course.
Jay S Keystone Tropical Disease Unit, University of Toronto, Ontario, Canada
For
other
The authors concluded that three of the mosquito species must have selected their hosts on a particular blend of human odours. The effect of expired carbon dioxide, a known mosquito attractant, was discounted since the three volunteers were of approximately the same weight, size, and age. Recent experiments using a wind-tunnel bioassay have suggested that human skin microflora might be responsible for producing compounds that attract mosquitoes.2 Human beings have been shown to have varying concentrations and species of skin bacteria resulting in the production of varying amounts of volatile substances that act as mosquito attractants. Earlier studies in blackflies, the "national insect" of Canadian wilderness areas, have shown that sweat, especially from below the waist, was attractive.3 Because trousers were more attractive to flies than were shirts, it has been suggested that the apocrine sweat glands of the groin region might be involved in producing the attractant compounds. Llactic acid and another unidentified compound, isolated from acetone washings to human skin, have been reported to act as attractants for mosquitoes-the differential attractiveness of human beings for Aedes aegypti mosquitoes was related to the amount of L-lactic acid recovered from skin washings, although lactic acid alone was not attractive without a carbon dioxide component in the airstream.’ A skin-produced mosquito attractant that is not dependent on carbon dioxide has also been identified.’ The receptor site for L-lactic acid seems to be a sensory apparatus on mosquito antennae.6 Before applying insect repellent to erogenous zones, readers should keep in mind that odour is not the only factor that attracts flying insects.’ Long-range attractant stimuli for mosquitoes may include movement and colour of clothing, especially dark colours. Carbon dioxide takes over the mid-range as the primary directing stimulus. At two.
1
Knols BGJ, de Jong R, Takken W. Differential attractiveness of isolated humans to mosquitoes in Tanzania. Trans R Soc Trop Med Hyg
2
Knols BGJ, de
1995; 89: 604-06.
Jong R, Takken W. Trapping system for testing olfactory responses of the malarial mosquito Anopheles gambiae in
a
wind tunnel. Med Vet Entomol 1995; 8: 386-88. 3 Thompson BH. Studies on the attraction of Simulium damnosum to its hosts. The nature of substances of the human skin responsible for attractant olfactory stimuli. Tropenmed Parasitol 1976; 27: 83-90. 4 Acree F, Turner RB, Gouck HK, Beroza M, Smith N. L-lactic acid: a mosquito attractant isolated from humans. Science 1968; 161: 1346-47. 5 Schreck CE, Smith N, Carlson DA, Price GD, Haile D, Goodwin DR. A material isolated from human hands that attracts female mosquitoes. J Chem Ecol 1970; 8: 429-38. 6 Davis EE, Sokolove PG. Lactic acid-sensitive receptors on the antennae of the mosquito Aedes aegypti. J Comp Physiol 1976; 105: 43-54. 7 Sutcliffe JF. Black fly host location: a review. Can Zool 1986; 64: 1041-53. 8 Port GR, Boreham PFL, Bryan JH. The relationship of host size to feeding by mosquitoes of the Anopheles gambiae Giles complex (Diptera culicidae). Bull Entomol Res 1980; 70: 133-44. 9 Gilbert IH, Gouck HK, Smith N. Attractiveness of men and women to Aedes aegypti and relative protection time obtained with DEET. Florida Entomol 1996; 49: 53-66. 10 Knols BGJ, Takken W, Charwood JD, de Jong R. Species-specific attraction of Anopheles mosquitoes (Dipeter: Culicidae) to different humans in south-east Tanzania. Proc Exp Appl Entomol 1995; 6: 201-06.
Ruling out Ingelfinger? world devoid of the "Ingelfinger rule". Could the medical community live comfortably without this grim warning from journal editors to prospective authors that a manuscript will be considered for publication only "if its substance has not been submitted or published elsewhere".’ The consequences of discarding Ingelfinger’s legacy would, argue many proponents of the rule, be catastrophic. Research would be disseminated by investigators according to the demands of the media, independent of careful scrutiny by journal editors and their peer reviewers. Once gathered and analysed, new data would be released to the press by status-seeking researchers and media-hungry institutions. Peer review would be subverted, fraudulent research might be encouraged, and the traditional processes of validating new work would be abandoned. Its proponents argue that the Ingelfinger rule protects the integrity of the scientific process, it is "essential to quality control", and it acts as a brake on investigators who "may unconsciously misrepresent their work or exaggerate its importance".’1
Imagine
a
1423
The rule expresses an agreement between the journal’s editor and the investigators. (It differs from the embargoan agreement between journalists and the editor-which aims to coordinate the simultaneous release of information contained in the journal to subscribers and the public.2) The Ingelfinger rule has been embraced by the International Committee of Medical Journal Editors’ and it has now found a new lease of life with the advent of the Internet. As with any good rule, there are exceptions. First, "presentations at scientific meetings and all published abstracts, as well as any media coverage based on them" are exempt.’ Second, data released as part of a national clinical alert are also acceptable, although authors may find that journal editors still object to full disclosure of data even in these circumstances. Third, there are results presented "in the course of governmental deliberations".’ And finally, data can be divulged by negotiation between authors and editors if "their findings are of such urgent concern that they should be released before publication".’ A recent example of this last escape clause was the early release of the finding of an association between vitamin A intake and cranial neural crest defects,6 which was agreed with the editors of the New England Journal of Medicine. The Lancet has recently drawn attention to the importance of linking public-health alerts to the simultaneous publication of peer-reviewed datawhich can be achieved by rapid peer review and an efficient publication process. But I find it hard to counter the view of Steven Rosenberg,8 who has written persuasively that "I think this whole involvement of journals in trying to control what doctors and scientists say to the press is wrong ... The journal should be publishing a scientific or medical article strictly on its merit: if it’s got merit, it should be published and, if not, it shouldn’t. Whether someone has talked to the press about it before shouldn’t play a role". In two articles, the second of which appears in this week’s issue, Lawrence Altman, medical correspondent of the New York Times, constructs the history of the Ingelfinger rule and examines the validity of the assumptions that underlie it. He finds the key premise supporting the argument for this partial gagging clause on researchers-namely, the power of peer review to validate a research paper-to be wanting in credibility. This observation is not new; although those of us who handle peer review know how much manuscripts change during their review. The lack of clear proof for the value of this process remains the impetus behind research into journal activities. Ingelfinger would surely have countered that a newspaper reporter should be expected to squeal at the editor’s prohibitive incursion into journalistic territory. But Altman also levels a more serious charge: that the journal editor’s role, as Ingelfinger admitted, is selfserving, embodying the commercial need of a journal to control the dissemination of research information. Ingelfinger acolytes might argue that this challenge merely reflects the healthy competition that exists between journalists and editors, both groups wishing to scoop the other. Publication in a peer-reviewed journal does not guarantee truth, as numerous examples of published fraudulent research prove.9 The ultimate validity of a
1424
research paper depends on the reproducibility of its results. Editorial review, external peer review, and subsequent published correspondence are critical filters in the process of validation but they can provide only incomplete quality control. Validation is not an event that is governed by journal editors, it is an iterative process of careful analysis and attempts at experimental refutation. Is it time to revoke the Ingelfinger rule? For those who believe that the rule reflects responsible editorial practice and a concern for quality, and does no harm, the answer will clearly be no. But those who see publication in a journal as only one small part of the scientific process, and one with no intrinsic claim to truth, may be less certain. One might predict that after an interval during which some researchers will be tempted to approach journalists directly before submitting their work to a scientific journal, the lessons of hyped reports and misleading interpretations are likely to encourage authors to adopt a policy of self-censorship until final publication. Selfregulation seems preferable to threats by editors to deny
publication. For research that bears directly on public-health issues, such as the safety of a drug, the responsible course of action is to publish, simultaneously with the alert, data on which the warning has been based. But for the vast majority of research, why should journal editors attempt to exert decisive control over its release? The commercial argument fails not only because there will always be an archival need, print or electronic, for journals but also because most research will be of little immediate interest to journalists and the public. And the personality of many journals, which secures their loyal readership, depends on more than the publication of primary research alone. With arguments such as these so finely balanced, The Lancet wishes to place a serious question mark over the Ingelfinger rule and to invite comment from readers, including researchers, editors, and journalists, as to the contemporary value of this injunction. My inclination is to rescind the rule, although this action would have little effect on authors if other journals chose to maintain their strict line. I cannot conceive of an instance when we would reject a paper only because of its previous publicity. Perhaps the question boils down simply to this: can editors trust investigators to report their research responsibly, and if not, why not? Richard Horton The Lancet, London, UK 1.
Angell M, Kassirer JP.
The
Ingelfinger rule revisited. N Engl J Med
1991; 325: 1371-73. 2. Kassirer JP, Angell M. Violations of the embargo and a new policy on early publicity. N Engl J Med 1994; 330: 1608-09. 3. International Committee of Medical Journal Editors. Uniform
4.
requirements for manuscripts submitted to biomedical journals. Philadelphia: American College of Physicians, 1994. Kassirer JP, Angell M. The Internet and the Journal. N Engl J Med 1995; 332: 1709-10.
5.
6. 7.
8.
9.
Altman LK. Doctors are warned about eye treatment. New York Times 1995; October 11: A17. Choo V. High-dose retinol associated with birth defects. Lancet 1995; 346: 1027. Editorial. Sensible alerts. Lancet 1995; 346: 1569. Cantigny conference series. Medicine and the media: a changing relationship. Chicago: Robert R McCormick Tribune Foundation, 1994: 20. Editorial. Dealing with deception. Lancet 1996; 347: 843.